Interferons have been shown to protect continuous cell lines against human immunodeficiency virus (HIV) infection in vitro. Using normal human macrophages, we have shown that this protection is essentially complete. However, relatively little is known about the ways in which interferons work against HIV. We now propose to define the mechanisms of interferon protection against HIV in macrophages, a relevant and technically ideal cell type for such experiments. Also, we will examine whether or not macrophages already infected by HIV respond to interferons in the same manner as their uninfected counterparts. Additionally, we found that the functional abilities of macrophages are generally undisturbed by HIV infection, with the exception that they resist secondary infection with vesicular stomatitis virus (VSV). Although VSV is not an important human pathogen, we hope that the elucidation of this HIV effect will reveal unsuspected aspects of HIV replication in macrophages. Finally, we will examine the possibility that dead HIV-Infected cells may still have infectious potential. These studies will test the assumption (implicit in several vaccine and immunological strategies for dealing with HIV infection) that killing HIV-infected cells will eliminate the virus from the body. Since macrophages engulf cellular debris, it is important to determine whether or not HIV genetic information escapes digestion in these scavenger cells. Taken together, these studies will help to elucidate the contribution of macrophages to the immune system and the effects of HIV upon them. Additionally, basic studies on the effects of interferons against HIV may contribute to the use of these agents in the therapy of HIV infection.